Ding Bisha, Fan Weimin, Lou Weiyang
Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China.
Program of Innovative Cancer Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang University, Hangzhou 310003, Zhejiang, China.
Mol Ther Nucleic Acids. 2020 Sep 16;22:445-455. doi: 10.1016/j.omtn.2020.09.007. eCollection 2020 Dec 4.
Increasing circular RNAs (circRNAs) have been reported to act as key players in human malignancies. However, the expression, role, and mechanism of circRNAs in HCC are not well elucidated. In this study, some differentially expressed circRNAs (DECs) between hepatocellular carcinoma (HCC) and normal tissues were identified using three circRNA microarrays (Gene Expression Omnibus [GEO]: GSE78520, GSE94508, and GSE97332). Twenty-one DECs were found to be commonly upregulated in all the three datasets. Among the 21 DECs, hsa_circ_0001955 ranked as the top three most upregulated DECs in GEO: GSE78520, GSE94508, and GSE97332. Moreover, hsa_circ_0001955 expression in HCC cells and tissues was significantly higher than that in corresponding normal controls. Functional experiments revealed that knockdown of hsa_circ_0001955 markedly inhibited proliferation, migration, and invasion of HCC, and its overexpression led to the opposite effects. hsa_circ_0001955 was mainly located in the cytoplasm, in which hsa_circ_0001955 could directly bind to miR-145-5p. miR-145-5p was downregulated in HCC, and its expression was negatively linked to hsa_circ_0001955 expression. Furthermore, we identified that NRAS was a downstream direct target of the hsa_circ_0001955/miR-145-5p axis in HCC. Collectively, our findings demonstrate the oncogenic roles of the hsa_circ_0001955/miR-145-5p/NRAS axis in HCC, which may represent a potential therapeutic target for HCC.
越来越多的环状RNA（circRNA）被报道在人类恶性肿瘤中起关键作用。然而，circRNA在肝癌中的表达、作用及机制尚未完全阐明。在本研究中，我们使用三个circRNA微阵列（基因表达综合数据库[GEO]：GSE78520、GSE94508和GSE97332）鉴定了肝细胞癌（HCC）与正常组织之间一些差异表达的circRNA（DECs）。发现21种DECs在所有三个数据集中均普遍上调。在这21种DECs中，hsa_circ_0001955在GEO：GSE78520、GSE94508和GSE97332中上调程度排名前三。此外，hsa_circ_0001955在HCC细胞和组织中的表达明显高于相应的正常对照。功能实验表明，敲低hsa_circ_0001955可显著抑制HCC的增殖、迁移和侵袭，而过表达则产生相反的效果。hsa_circ_0001955主要位于细胞质中，在细胞质中hsa_circ_0001955可直接与miR-145-5p结合。miR-145-5p在HCC中表达下调，其表达与hsa_circ_0001955的表达呈负相关。此外，我们确定NRAS是HCC中hsa_circ_0001955/miR-145-5p轴的下游直接靶点。总的来说，我们的研究结果证明了hsa_circ_0001955/miR-145-5p/NRAS轴在HCC中的致癌作用，这可能代表了HCC的一个潜在治疗靶点。
